Excess insulin responses to glucose load have recently been reported in patients with syndrome X (effect angina, ischemia-appearing ST responses to exercise, normal coronary arteries). Because insulin may have vascular effects that might account for abnormal cardiac responses to exercise, we measured insulin responses to glucose load in 36 patients and compared that insulin responses to 22 healthy controls of similar age, gender, and weight. The impact of insulin on vascular function was assessed by measuring forearm vascular resistance at rest, and following glucose load when insulin levels are highest. Forearm vascular resistance was measured non-invasively by strain gauge plethysomography and cuff blood pressure measurements. Although fasting insulin was similar for patients with chest pain and normal coronary angiograms and for controls (21+/-17 vs. 17+-10 muU/ml, patients had a higher peak insulin response (176+-99 vs. 107+-44 muU/ml, p<0.01) to an oral glucose load (75 grams). However, the forearm vascular resistance both at baseline and after glucose load was no different between the two groups. Further, there was no correlation between the magnitude of insulin response to glucose load, and the presence of hypertension, evidence for coronary vascular dysfunction, or the EKG response to exercise. Thus, although hyperinsulinemia is common in patients with chest pain and normal coronary arteries, the impact of increased insulin levels in the coronary and systemic vasculature is unclear.